This invention relates to acridin derivatives of general formula I ##STR2##
or pharmaceutically acceptable salts thereof, and relates to a method of producing them and to their use as drugs.
Classical opioids such as morphine are used for the therapy of severe and very severe pain. Their use is limited, however, by their known side effects, e.g. respiratory depression, vomiting, sedation and obstipation, and by the development of tolerance. Moreover, they are less effective for neuropathic or incidental pain, from which tumour patients suffer in particular.
Opioids develop their analgesic effect by binding to membrane receptors, which form part of the family of what are termed G protein-coupled receptors. The biochemical and pharmacological characterisation of subtypes of these receptors has shown that subtype-specific opioids exhibit a spectrum of effects and side-effects which is different to that of morphine for example. Whereas morphine binds selectively to what are termed .mu.-receptors, endogenous enkephalins have been characterised as .delta.-selective peptides. In the meantime, other pharmacological investigations have indicated that a plurality of subtypes of these opioid receptors (.mu..sub.1, .mu..sub.2, .kappa..sub.1, .kappa..sub.2, .kappa..sub.3, .delta..sub.1 and .delta..sub.2) probably exist.
Knowledge of the physiological importance of .delta.-receptor-selective substances has essentially been widened by the development of the non-peptidic antagonist naltrindol. In the meantime, it has been ascertained that .delta.-agonists exhibit an autonomous antinociceptive potential. In addition to a multiplicity of experimental studies on animals, an investigation has also been performed in which the peptidic agonist D-alanine.sup.2 -D-leucine.sup.5 -enkephalin (DADL) was used on cancer patients on whom morphine no longer had an analgesic effect. When administered intrathecally, DADL exhibited a long-term analgesic effect. Moreover, .delta.-agonists differ from .mu.-agonists as regards their interaction with the "endogenous opioid antagonist" cholecystokinin (CCK).